Bronchodilator Effects and Safety of Glycopyrronium Bromide (25 ug and 50 ug o.d.) in Asthma

A Multicenter, Randomized, Double-blind, Placebo-controlled 3-period Complete Cross-over Study to Assess the Bronchodilator Effects and Safety of Glycopyrronium Bromide (NVA237) (25 ug and 50 ug o.d.) in Asthma Patients.

The purpose of this trial is to characterize the bronchodilator effects and safety of 25 ug and 50 ug o.d. NVA237 (glycopyrronium bromide) doses compared to placebo in asthma patients

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: NVA237 (glycopyrronium bromide); Drug: Placebo

Detailed Description

This study uses a randomized, double-blind, placebo controlled, 3-period cross-over clinical trial design. During a screening epoch patient eligibility will be assessed. The screening epoch will be followed by a 21-day Run-in epoch during which patients will continue their inhaled corticosteroids use but be withdrawn from LABA-treatment and switched to short-acting bronchodilator-rescue medication. After the Run-in period patients will be randomized to one of the 6 treatment sequences and enter the first 7-day study treatment period. Treatment period one is followed by a 10 to 14 days washout period after which patients begin the second 7-day treatment period which is then followed by a second 10 to 14 days washout period followed by the third 7-day treatment period. At the end of each treatment period spirometry will be performed to assess the primary endpoint in terms of trough FEV1. The study population will consist of approximately 144 patients with asthma who have been treated in a stable regimen of ICS/LABA for at least 4 weeks prior to screening.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Erpent, Belgium, 5100
    • Novartis Investigative Site
  • Hasselt, Belgium, 3500
    • Novartis Investigative Site
  • Mechelen, Belgium, 2800
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10119
    • Novartis Investigative Site
  • Frankfurt, Germany, 60596
    • Novartis Investigative Site
  • Grosshansdorf, Germany, 22927
    • Novartis Investigative Site
  • Lubeck, Germany, 23552
    • Novartis Investigative Site
  • Wiesbaden, Germany, 65187
    • Novartis Investigative Site
• Japan
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 169-0073
      • Novartis Investigative Site
    • Toshima-ku, Tokyo, Japan, 171-0014
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, LV 1002
    • Novartis Investigative Site
  • Riga, Latvia, LV-1038
    • Novartis Investigative Site
  • LVA
    • Daugavpils, LVA, Latvia, LV-5417
      • Novartis Investigative Site
• Lithuania
  • Klaipeda, Lithuania, LT-92231
    • Novartis Investigative Site
  • Klaipeda, Lithuania, LT-92288
    • Novartis Investigative Site
• United States
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Novartis Investigative Site
  • New Jersey
    • Skillman, New Jersey, United States, 08558
      • Novartis Investigative Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Novartis Investigative Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Novartis Investigative Site
  • Texas
    • El Paso, Texas, United States, 79903
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female adult patients aged >= 18 or =< 65 years
• Patients with a diagnosis of asthma for a period of at least 1 year receiving daily treatment of ICS/LABA in a stable regimen for >= 4 weeks
• Pre-bronchodilator FEV1 of >= 50% and =< 80% of the predicted normal value and an increase in FEV1 of 12% and >= 200 ml during reversibility testing

Key Exclusion Criteria:

• Patients who have had an asthma exacerbation that required either treatment with systemic corticosteroids for at least 3 days, or an emergency room visit, or hospital treatment within 6 weeks prior to screening and patients with a history of life-threatening asthma attacks
• Patients who have had a respiratory tract infection within 4 weeks prior to screening.
• Patients who have smoked or inhaled tobacco products within the past 6 month of screening.
• Patients with a history of chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, bronchiectasis, sarcoidosis, interstitial lung disease, cystic fibrosis, and tuberculosis (unless tuberculosis is confirmed as no longer active by imaging).
• Patients on Maintenance Immunotherapy (desensitization) for allergies for at least 3 months prior to Run-in who are expected to change therapy throughout the course of the study.
• Patients who during the Run-in period are shown to be intolerable to LABA withdrawal.
• Patients who have discontinued LAMA therapy in the past (e.g. due to intolerance or perceived lack of efficacy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1(NVA237 50 ug/NVA237 25 ug/placebo); Treatment sequence: NVA 237 50 ug, 25 ug and placebo	Drug: NVA237 (glycopyrronium bromide); In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose; Drug: Placebo; In each treatment arm, patient will receive placebo
Other: 2(NVA237 50 ug/placebo/NVA237 25 ug); Treatment sequence: NVA 237 50 ug, placebo and 25 ug	Drug: NVA237 (glycopyrronium bromide); In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose; Drug: Placebo; In each treatment arm, patient will receive placebo
Other: 3 (NVA237 25 ug/NVA237 50 ug/placebo); Treatment sequence: NVA237 25 ug, 50 ug and placebo	Drug: NVA237 (glycopyrronium bromide); In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose; Drug: Placebo; In each treatment arm, patient will receive placebo
Other: 4 (NVA237 25 ug/placebo/NVA237 50 ug); Treatment sequence: NVA 237 25 ug, placebo and 50 ug	Drug: NVA237 (glycopyrronium bromide); In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose; Drug: Placebo; In each treatment arm, patient will receive placebo
Other: 5 (placebo/NVA237 50 ug/ NVA237 25 ug); Treatment sequence: Placebo, NVA237 50 ug and 25 ug	Drug: NVA237 (glycopyrronium bromide); In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose; Drug: Placebo; In each treatment arm, patient will receive placebo
Other: 6 (placebo/ NVA237 25 ug/NVA237 50 ug); Treatment sequence: placebo, NVA237 25 ug and 50 ug	Drug: NVA237 (glycopyrronium bromide); In each treatment arm, patient will receive NVA237 (glycopyrronium bromide) 25 ug and 50 ug dose; Drug: Placebo; In each treatment arm, patient will receive placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough FEV1 After One Week of Treatment, Point Estimate	To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared to placebo in terms of trough FEV1 (mean of 23h 15 min and 23 h 45 min post -dose) following 1 week of treatment in the respective treatment period. Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 15 min and 23h 45 min post dose.	Following 1 week of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC (5 Min-1 h) After One Week of Treatment	To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 5min-1h)	Following 1 week of treatment
FEV1 AUC (5 Min-4 h) After One Week of Treatment	To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 5min-4h)	Following 1 week of treatment
FEV1 AUC (5 Min - 23 h 45 Min) After One Week of Treatment	To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Standardized FEV1 AUC following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day AUC (5 min - 23 h 45 min)	Following 1 week of treatment
Peak FEV1 During 4 Hours Post-dose After 1 Week of Treatment	To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of Peak FEV1 following 1 week of treatment in the respective treatment period. FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect following 1 week of treatment was defined as the maximum FEV1 during the first 4 hour on that day.	Following 1 week of treatment
Trough Forced Vital Capacity (FVC) After 1 Week of Treatment	To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FVC following 1 week of treatment in respective treatment period. Trough Forced Vital Capacity (FVC) following 7 Days. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry	Following 1 week of treatment
Percent Change From Baseline in FEV1/FVC Ratio	To evaluate the bronchodilator effects of NVA237 (25 ug and 50 ug) compared with placebo in terms of FEV1/FVC ratio following 1 week of treatment in respective treatment period	Following 1 week of treatment
Mean Morning Peak Expiratory Flow (PEF) Following the 1-week Treatment Period	A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value	Following 1 week of treatment
Mean Evening Peak Expiratory Flow Rate (PEF) Following 1-week Treatment	A Peak Expiratory Flow (PEF) meter was distributed to patients at Visit 1, to be used to measure PEF twice-daily as directed. During the Screening and Treatment Periods, PEF was measured in the morning and evening every day. the morning PEF was performed within 15 minutes after waking, and the evening PEF approximately 12 hours later. Patients were encouraged to perform morning and evening PEF measurements before the use of any LABA or rescue medication. The highest of 3 values was recorded as the daily personal best. The personal best was used to calculate the mean morning PEF and mean evening PEF value collected between assessment Visits. LS Mean of change from baseline in mean morning PEF is calculated with the ANCOVA model using treatment, stratification group, dosing schedule, gender, center grouping, smoking status, and baseline mean morning PEF as covariates	Following 1 week of treatment
Mean Daily Number of Puffs of Rescue Medication During 1 Week of Treatment	A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours. daytime and nighttime (combined) number of puffs is defined as the average of the respective number of puffs.	Following 1 week of treatment

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2017
• Primary Completion (Actual): December 29, 2017
• Study Completion (Actual): December 29, 2017

Study Registration Dates

• First Submitted: April 24, 2017
• First Submitted That Met QC Criteria: April 28, 2017
• First Posted (Actual): May 3, 2017

Study Record Updates

• Last Update Posted (Actual): January 16, 2019
• Last Update Submitted That Met QC Criteria: January 15, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: asthma,; allergic asthma,; allergy triggered asthma,; reactive asthma,; asthma attack,; difficulty breathing; glycopyrronium bromide; NVA237,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Anticonvulsants; Glycopyrrolate; Bromides
• Other Study ID Numbers: CQVM149B2204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No